The pineal gland of rodents has long been known to produce a regression of the reproductive system of animals placed in a short photoperiod or that are blinded. Though this effect was orginally described in hamsters, similar findings have been observed in rats if, in addition to blinding the animals are rendered anosmic by olfactory bulbectomy. Part of the mechanism of pineal-induced gonadal regression is an inhibition of the secretion of the pituitary hormone prolactin (PRL). In fact, the pineal gland has been shown to produce an inhibition of not only PRL secretion but also PRL synthesis and storage within the cells as well as a diminution in cell size and total pituitary PRL cell number. Since the pineal can exert such a strong inhibition on normal PRL cells it is of interest to determine the influence of the gland and its hormones on adenomatous PRL cells. The studies proposed here will 1) investigate the influence of the pineal on the induction and growth of diethylstilbestrol(DES)-induced prolactinomas in blind-anosmic Fisher 344 female rats; 2) determine if exogenous administration of the pineal hormone melatonin can affect tumor induction and growth, and 3) examine the interactions of the pineal and its hormones with the dopaminergic control of the PRL cells. The state of activity of the PRL cells under the various treatment regimens will be evaluated in several ways: we will measure changes in pituitary weight, pituitary DNA, RNA and protein content, PRL synthesis (assessed by the in vitro incorporation of 3H-leucine into PRL), pituitary storage of PRL and PRL release into the circulation. Additionally, both transmission electron microscopy and light microscopic immunocytochemistry for PRL will be used to assess morphological changes in individual PRL cells and the entire pituitary population of these cells, respectively. The information derived from these studies may eventually lead to a new, alternative or conjunctive, therapy using pineal hormones for the control of prolactinomas, the accompanying hyperprolactinemia and associated infertility.